‘Master Protocol’ is bringing clinical trial design into the 21st century

Published: June 12th, 2013

All new cancer drugs are developed through clinical trials. Clinical trials provide essential information for the FDA and doctors to make informed decisions about whether new drugs are safe and effective. But clinical trials face a number of hurdles including cost, patient participation, and effective design. The new “Master Protocol” spearheaded by Friends of Cancer Research aims to modernize and streamline the system to address all three.

The clinical stage of the drug development pipeline is clearly the costliest. Late stage clinical trials can cost upwards of $50 million to $100 million – that’s testing just one new treatment. There are currently 1,320 open clinical trials for lung cancer treatment. At the low estimate, that’s $66 billion invested from both public and private sources. Yet, the vast majority of clinical trials end without a drug approval.

Clinical trials also face difficulties recruiting participants. Only 1,864 lung cancer patients were enrolled in NCI-sponsored treatment clinical trials in 2012, compared to the 226,000 people diagnosed that year. Many trials will go on for years, trying to reach the patient enrollment numbers needed for proper statistical analysis to guide the FDA. This results in increased costs for trial sites to keep the trials open, and prevents the potentially life-saving treatments from being available to all lung cancer patients.

Clinical trial design is also facing logistical problems. The recent successful lung cancer drug clinical trials have incorporated biomarkers, enabling the trial to focus on patients most likely to respond to the investigational treatment. This means patient populations are getting even smaller. For example, the ALK biomarker is found in only 3-7% of non-small cell lung cancer patients. Additional biomarkers are being identified in even smaller patient populations. With lung cancer now considered a collection of rare diseases, how can we recruit enough patients necessary for a completed clinical trial?

The lung cancer Master Protocol is changing trial design to address these issues, bringing multiple companies together to test multiple experimental drugs for lung cancer in late-stage clinical trials using one master protocol design. The initiative has gained buy-in from the NCI and the FDA as well as pharmaceutical companies. The initial protocol will test six lung cancer drugs, with the ability to add more later. Rather than being tested multiple times for each trial, patients will be screened for all applicable biomarkers and assigned to the appropriate arm of the trial. Trial costs could be cut in half using this centralized system.

There are many potential benefits, and also many issues still to be addressed. Companies have concerns regarding proprietary information and competition. The logistics of a massive trial may prove difficult to manage. Yet at this time, the pros seem to far outweigh the cons. Clinical trials are essential to drug development. Without effective and efficient clinical trials, our investment in research will never translate to new treatments for lung cancer patients.